Granzymes are serine proteases present in secretory granules of cytolytic T cells and natural killer (NK) cells (Bleackley et al, 1988, Jenne, 1988). Granzyme B and A along with perforin have been implicated in cell-mediated cytotoxicity (Bleackley et al, 1988, Jenne, 1988). These granzymes were purified from human T cell lines and from short-term cultures of activated human PBMCs (Hameed et al, 1988, Krahenbuhl et al, 1988, Poe Ct al, 1998, Poe et al, 1991).
Recently, the three dimensional structure of Granzyme B was established (Waugh et al, 2000). Granzyme B has an Aspase activity (Poe et al., 1991, Powers and Kam, 1995) whereas granzyme A has tryptase activity (Peitsh and Tschopp, 1994). Much progress has been made in understanding the molecular mechanisms of granzyme B associated apoptosis in target cells (Russel and Timothy, 2002). Granzyme B can cause apoptosis of target cells by both caspase dependent and caspase independent mechanisms (Talania, 1997, Thomas et al, 2000, Alimonti J B, 2001).
Very little is known about the mechanism of granzyme A in inducing cell death. (Pinkoski et al, 2003). Although granzyme H was identified in activated T-cells and found to have chymase activity, nothing is known about its role in target cell death (Haddad, 1991; Edwards et al., 1999).